3334
J. Am. Chem. Soc. 1983, 105, 3334-3336 300
tance of using the tensorial shifts over the traditional isotropic chemical shift obtained in liquids. Not only does one obtain three times more information but very important directional features also are obtainable. It is hoped that these results will contribute to a greater appreciation of the importance of three-dimensional chemical shift data among chemists interested in structurally selective chemical properties or processes. Furthermore, it should warn against overinterpretation of isotropic chemical shift parameters.
e 0 0
-
250
c
E 200 0 b
Li
Acknowledgment. This work was sponsored by a grant from the Chemistry Section of the National Science Foundation (CHE
150
?i
8000256).
8 a
Registry No. 1, 26811-28-9; 2, 71-43-2; 3, 12127-83-2.
.i B
loo
50
1
2
3
0.8571
1.0
1.20
0
n - electron charge
Figure 2. Tensorial chemical shifts for tropylium cation (l),benzene (2), and cyclopentadienide anion (3) as a function of *-electron charge.
values for 1 and 3 are reported here for the first time. Our values for 2 differ from those reported recently'O by more than our experimental error of f3 ppm. It is noted that our trace agrees within f3 ppm with the isotropic liquid values as do the corresponding trace values for the two ions. Our referencing technique involves using an external sample of Me4Si and therefore may introduce an error as large as f3 ppm. Figure 2 clearly indicates that u l l , uz2,d,and to a reasonable degree piso are dependent upon q,. The plot of q3, however, shows no simple dependence upon q,, and the relationship is not even monotonic. The negligible dependence upon q, in u33compared with u l I and uZ2makes the trace less sensitive to q, than the two more responsive components. Waugh and co-workers4 have used charge-withdrawal arguments to rationalize the changes in tensorial shifts of alkylbenzenes complexes with Cr(CO)3. Such arguments are even more jusitified in the present case. The variations in the tensorial components reflect primarily the behavior of electrons located in the p orbitals oriented perpendicular to the component axis.5 The value of u33 is characteristic of saturated carbon atoms, and this is reasonable considering that it is determined primarily by the properties of electrons in the u bonds. Thus, uj3 is likely to be more sensitive to the strain in the C-C-C angle than to qr, upon which the original correlation for uisowas based.2 The q, will affect u33only through second-order charge-polarization effects upon the uelectron structure. Both u l I and uZ2are affected by changes in q, directly as the axes of these components lie in the molecular plane. They differ only in the manner in which they sample the u-electron distribution in the C-C and C-H bonds, respectively. Because both u l l and uzzdepend directly upon q,, the average, u', of these two shifts was calculated and is plotted against q, in Figure 2. A very linear relationship exists between d and q, with a slope for -218 ppm/e compared with the -160 ppm/e slope found for the isotropic shift in ref 2. Thus, the curvature in the plot of the isotropic shift largely arises from the u33contribution. This work supports the original premise that chemical shifts depend upon q, but refines the proposal to focus on only those shift components that reflect the very anisotropic charge distributions associated with charged aromatic systems. As chemical shielding is very sensitive to charge effects, such three-dimensional information is of the utmost importance in understanding this relationship. This work also graphically emphasizes the impor(10) Linder, M.; Hohener, A.; Emst, R. R. J . Magn. Reson. 1979,35, 379.
0002-7863/83/1505-3334$01.50/0
Biosynthesis of Mevinolin. Spectral Assignment by Double-Quantum Coherence NMR after High Carbon-13 Incorporation+ Jean K. Chan, Richard N. Moore, Thomas T. Nakashima, and John C. Vederas* Department of Chemistry, University of Alberta Edmonton, Alberta, Canada T6G 2G2 Received January 1 1 , 1983 Mevinolin (1),1$2a compactin (2),2b3cand analogues such as the
"
O
o
o
\ o,+"
-1 -2
R=CH3
R=H
corresponding 4a,S-dihydro derivatives2d,eare fungal metabolites that block isoprenoid bio~ynthesis.~,~ Competitive inhibition of the key enzyme in the pathway, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase; E.C. 1.1.1.34),by the lactone-opened forms of these compounds decreases availability of mevalonate and thereby lowers plasma cholesterol levels in various mammals, including man.3*4 Since more than half of the 'Dedicated to Professor Christoph Tamm, University of Basel, on the occasion of his 60th birthday. (1) Mevinolin (1) from Aspergillus terreus& and monacolin K from Monascus ruber (Endo, A. J . Antibiot. 1979, 32, 852-854. Endo, A. Ibid. 1980, 33,334-336) appear to be the same compound;2ccompactin (2) is also known as ML-236B.*' (2) (a) Alberts, A. W.; Chen, J.; Kuron, G.; Hunt, V.; Huff, J.; Hoffman, C.; Rothrock, J.; Lopez, M.; Joshua, H.; Harris, E.; Patchett, A,; Monaghan, R.: Currie. S.: Stadev. E.: Albers-Schonbera. G.: Hensens. 0.:Hirshfield. J.: Hoogsteen, K.; Likih, J.; Springer, J. Pro:. Natl. Acad. Sci. U.S.A. 1980, 77, 3957-3961. (b) Brown, A. G.; Smale, T. C.; King, T. J.; Hasenkamp, R.; Thompson, R. H. J . Chem. SOC.,Perkin Trans. I 1976, 1165-1 170. (c) Endo, A.; Kuroda, M.; Tsujita, Y . J . Antibiot. 1976, 29, 1346-1348. (d) AlbersSchonberg, G.; Joshua, H.; Lopez, M. B.; Hensens, 0. D.; Springer, J. P.; Chen, J.; Ostrove, S . ; Hoffman, C. H.; Alberts, A. W.; Patchett, A. A. Ibid. 1981, 34, 507-512. (e) Lam, Y. K. T.; Gullo, V. P.; Goegelman, R. T.; Jorn, D.; Huang, L.; DeRiso, C.; Monaghan, R. L.; Putter, I. Ibid. 1981, 34, 6 14-6 16. (3) (a) Endo, A. Trends Eiochem. Sci. 1981, 6, 10-13. (b) Endo, A. Methods Enzymol. 1981, 720, 684-689. (4) (a) Kritchevsky, D.; Tepper, S. A,; Klurfeld, D. M. Pharmacol. Res. Commun. 1981, 13, 921-926. (b) Tobert, J. A.; Hitzenberger, G.; Kukovetz, W. R.; Holmes, I . B.; Jones, K. H. Atherosclerosis 1982, 41, 61-65. (c) Kroon, P. A.; Hand, K. M.; Huff, J. W.; Alberts, A. W. Ibid. 1982, 44, 41-48. (d) Tobert, J. A.; Bell, G. D.; Birtwell, J.; Kukovetz, W. R.; Pryor, J. S.; Buntmx, A,; Holmes, I. B.; Chao, Y . S.; Bolognese, J. A. J . Clin. Itwesr. 1982, 69, 913-919.
0 1983 American Chemical Society
J . Am. Chem. SOC.,Vol. 105, No. 10, 1983 3335
Communications to the Editor total human body cholesterol originates from de novo biosynthesis, such materials possess obvious potential in treatment of atherosclerosis and coronary heart d i ~ e a s e . ~Analogous effects on d o l i ~ h o lubiquinone,6 ,~ and insect juvenile hormone production,' as well as influences on plant root elongation,* also establish 1 and 2 as important biochemical tool^.^,^ Their unusual structures and biological significance have inspired totallo and partial" syntheses of compactin (2) and structural modification studies12 on mevinolin (1). In this communication we report the biosynthesis of mevinolin (1) in Aspergillus terreus ATCC 20542 from acetate and methionine using multiply labeled 13C,I S 0 , and 2H precursors. We also describe how recently developed N M R pulse sequences in combination with a high level of biosynthetic multiple labeling allow rapid assignment of I3C N M R spectra on the basis of carbon-carbon coupling. Since complete determination of N M R spectral positions is the usual prerequisite for stable isotope incorporation studies,I3 the IH N M R spectrum of mevinolin (1) was first assigned by using chemical shifts and selective homonuclear decoupling experim e n t ~ . ' ~However, subsequent examination of both broad band proton-decoupled and spin echo Fourier transform (SEFT)I5 I3C N M R spectra of 1 did not permit complete unambiguous resonance identification, even with selective heteronuclear ('H) decoupling experiments. The similarity of a number of carbon signals in multiplicity and I3C N M R chemical shift was unfortunately reflected by 'H N M R overlap of their attached hydrogen resonances. Recent development of double-quantum coherence N M R now allows determination of the carbon connectivity pattern by observation of natural abundance carbon-arbon coupling,16but often large quantities (0.5-1.0 g) of sample are required for spectral analysis. Application of such a two dimensional INADEQUATE e ~ p e r i m e n t ~to~ mevinolin ~ ~ ' ~ ' ~ (1) after heavy in-
-
I NH2
Figure 1. Table 1. 13C NMR Data of Mevinolin (1) Derived from Sodium [l-"C]-, [2-13C]-, and [l-13C,2H,]Acetatea
c enhancementb carbon
(5) Carson, D. D.; Lennarz, W. J. J . Biol. Chem. 1981,256,4679-4686. (6) Ranganathan, S.; Nambudiri, A. M. D.; Rudney, H. Arch. Biochem. Biophp. 1981, 210, 592-597. (7) Monger, D. J.; Lim, W. A.; Kezdy, F. J.; Law, J. H. Biochem. Biophys. Res. Commun. 1982, 105, 1374-1380. (8) Bach, T. J.; Lichtenthaler, H. K. Z . Naturforsch. C 1982,37C, 46-49. (9) (a) Ryan, J.; Hardeman, E. C.; Endo, A.; Simoni, R. D. J. Biol. Chem. 1981,256,6762-6768. (b) Chin, D. J.; Luskey, K. L.; Anderson, R. G. W.;
Faust, J. R.; Goldstein, J. L.; Brown, M. S.Proc. Natl. Acad. Sci. U.S.A. 1982, 79, 1185-1 189. (c) Quesney-Huneeus, V.; Galick, H. A.; Siperstein, M. D.; Erickson, S. K.; Spencer, T. A.; Nelson, J. A. J . Biol. Chem. 1983, 258. 378-385. (10) (a) Wang, N. Y.; Hsu, C. T.; Sih, C. J. J . Am. SOC.1981, 103, 6538-6539. (b) Hirama, M.; Uei, M. Ibid. 1982, 104, 4251-4253. (c) Girotra, N. N.; Wendler, N. L. Tetrahedron Lett. 1982, 23, 5501-5504. (d) Hsu, C. T.; Wang, N. Y . ;Latimer, L. H.; Sih, C. J. J . Am. Chem. SOC.1983, 105, 593-601. (e) Grieco, P. A,; Zelle, R. E.; Lis, R.; Fin, J. Ibid. 1983, 105, 1403-1 404. (1 1) Lactone portion: (a) Danishefsky, S.;Kerwin, J. F., Jr.; Kobayashi, S.J . Am. Chem. SOC.1982, 104, 358-360. (b) Prugh, J. D.; Deana, A. A. TetrahedronLett. 1982.23, 281-284. (c) Yang, Y. L.; Falck, J. R. Ibid. 1982, 23,4305-4308. Hexahydronaphthalene portion: (d) Funk, R. L.; Zeller, W. E. J. Org. Chem. 1982, 47, 18C-182. (e) Deutsch, E. A.; Snider, B. B. Ibid. 1982, 47, 2682-2684. (f) Heathcock, C. H.; Taschner, M. J.; Rosen, T.; Thomas, J. A.; Hadley, C. R.; Popjak, G. Tetrahedron Lett. 1982, 23, 4747-4750. (g) Anderson, P. C.; Clive, D. L. J.; Evans, C. F. Tetrahedron
Lett., in press. (12) (a) Lee, T. J.; Holtz, W J.; Smith, R. L. J . Org. Chem. 1982, 47, 475C-4757. (b) Willard, A. K.; Smith, R. L. J . Labelled Compd. Radiopharm. 1982, 19, 337-344. (13) (a) Garson, M. J.; Staunton, J. Chem. SOC.Rev. 1979, 539-561. (b) Wehrli, F. W.; Nishida, T. Prog. Chem. Org. Nut. Prod. 1979, 36, 1-229. (14) The 'H NMR assignment of mevinolin (1) has been partially rep o r t d Z a For complete spectral assignment see supplementary material. (15) (a) Brown, D. W.; Nakashima, T. T.; Rabenstein, D. L. J . Magn. Reson. 1981,45, 302-314. (b) Bendall, M. R.; Pegg, D. T.; Dcddrell, D. M.; Johns, S.R.; Willing, R. I. J. Chem. SOC.,Chem. Commun. 1982, 1138-1 140. (16) (a) Bax, A.; Freeman, R.; Kempsell, S.P. J . Am. Chem. SOC.1980, 102, 4849-4851. (b) Bax, A.; Freeman, R.; Frenkiel, T. A. Ibid. 1981, 103, 2102-2104. (c) Neszmelyi, A.; Lukacs, G. J . Chem. SOC.,Chem. Commun. 1981, 991-1001. (d) Bax, A.; Freeman, R.; Frenkiel, T. A.; Levitt, M. H. J. Magn. Reson. 1981, 43, 478-483. (e) Turner, D. L. Ibid. 1982, 49, 175-178. (f) Robinson, J. A.; Turner, D. L. J . Chem. SOC.,Chem. Commun. 1982, 148-151. (9) Ashworth, D. M.; Robinson, J. A.; Turner, D. L. Ibid. 1982,491-493. (h) Freeman, R.; Frenkiel, T.; Rubin, M. B. J . Am. Chem. SOC.1982, 104, 5545-5547. (i) Neszmelyi, A.; Hull, W. E.; Lukacs, G. Tetrahedron Lett. 1982, 23, 5071-5074. (j)Pinto, A. C.; Do Prado, S.K.; Filho, R. B.; Hull, W. E.; Neszmelyi, A.; Lukacs, G. Ibid. 1982, 23, 5267-5270.
CH3COONa
A CH3SCH2CH2CHCOOH
S
1 2
36.7 30.7
2-Me 3 4 4a 5 6 6-Me 7 8 8a 9 10 11 12 13 14 15 1' 2' 2'-Me 3'
13.9 33.1 28.4 31.6 29.6 21.5 22.9 32.8 68.0 37.4 24.3 33.0 75.7 36.2 62.6 38.7 70.7 76.9 41.6 16.3 26.8
4'
11.7
[l13C]
[213C]
2.4
[ l-13C,2H,]acetate incorp 2H:1HC
ASd
24:76
4.1
-0.25, -0.17, -0.082e 2.3 3.1
76: 8 : 8 : 8e 0: 100
3.3 4.4 3.0 5.2
0:lOO
3.2 1.4
45:55
4.6 4.1
+0.013 -0.096 2.2
80:20
2.4
50:50
3.4
50:50
4.6
-0.06
7.7
-0.12
2.8 2.4
+0.04 +0.018 2.9
15 :25
4.4 2.9
-0.21,-0.14, -0.071e 76:8:8:8e
For spectral conditions see ref 17. Ratio of carbon signal intensities for enriched and natural abundance sample measured under identical conditions. Ratio of carbon peak areas for pisotope shifted signals. @-Isotopeshifts due to 2H are given in ppm. e CD,.CHD,:CH,D:CH,. a
corporation'8 of doubly labeled sodium [ 1,2-13C2]acetate19 by A . terreus permitted complete I3C N M R assignment with only 20 mg of sample because of a 200-fold increase in the relative intensity of coupled carbon signals (from 0.01% to about 2% for each coupled pair of carbon atoms). The pulse feedingI8 also led to multiple acetate incorporations within a single molecule of mevinolin (l),thereby allowing observation of I3C-l3C coupling between carbons of neighboring biosynthetic units and establishing (17) All I3C NMR spectra were obtained at 100.6 MHz on a Bruker WH400 spectrometer using ca. 0.1 M solutions of mevinolin (1) in CDC13 (5-mm tubes) with MelSi internal standard at 25 OC. Two-dimensional INADEQUATE experiments followed literature procedures16bsioptimized for 'JCC= 42 Hz and accumulated (128 scans) with a 5-s recycle delay time by using spectral widths of *3520 Hz (70 ppm) and 3496 Hz with a data block of (148 X IK). (18) Incorporation rates were estimated by mass spectral examination of the molecular ion regions of labeled and unlabeled samples, as well as by comparison of 13C NMR spectra. See supplementary material for experimental details of fermentations. (19) Cambridge Isotope Laboratories, Cambridge, MA: 97% "C,.
3336
J . Am. Chem. SOC. 1983, 105, 3336-3337
the complete connectivity pattemZ0 This technique of spectral assignment requires no knowledge of the biosynthetic distribution of label since it depends exclusively on increasing the level of I3C in the molecule. However, intact biosynthetic units can still be identified because there is a much higher level of coupled signals between carbons comprising them if multiply 13C-labeled precursors are used.21 Bacher, Floss, and co-workers recently demonstrated22the utility of double-quantum coherence N M R for biosyntheses employing [ U - 1 3 C , ] g l ~ c ~ as~ae p r e s ~ r s o r . ~ ~ Incorporations18of sodium [ l-I3C]acetate, sodium [2-I3C]acetate, and [methyl-13C]methionine followed by I3C N M R analysis showed that the main portion of mevinolin (1) consists of a plyketide chain of nine intact acetate units with a methionine-derived methyl group at C-6 (Figure 1). Interestingly, the a-methylbutyryl side chain is constructed in an analogous fashion. Recent methods to detect oxygen-1SZ4 or d e ~ t e r i u m ' ~by~ isotope J~ shifts induced in 13CN M R provide mechanistic information by limiting possible intermediate oxidation states and revealing precursor bonds to oxygen or hydrogen that remain intact in the product. Administration18 of sodium [ 1-13C,180z]acetate24b to cultures of A. terreus followed by both normal and SEFT 13C N M R analysisz4& of the resulting mevinolin (1) showed extensive labeling of the doubly bonded oxygen at C-1' (isotope shift 0.038 ppm). Even though 13C incorporation was high (2-7-fold peak enhancement), the amount of oxygen-18 at other expected sites such as (2-11, C-13, and C-15 was less than 5% of the carbon labeling. We are currently investigating the problem of solvent-exchange during biosynthesis. Incorporation of sodium [ 1'3C,zH3]acetate and 13C N M R examination of the @-isotope shifts25in mevinolin (1) indicated high 2Hretention at all expected sites except C-3 and C-6 (Table I). Since the @-isotopeshifts may be upfield, downfield, or possibly there is a small chance that these carbons bear deuterium, but most probably the biogenesis of 1 results in hydrogen loss at these positions. The presence of species bearing three deuteriums at C-4' and at the C-2 methyl identifies these carbons as starter units of the polyketide chains. These observations were confirmed by 2H N M R of mevinolin (1) derived from sodium [ZH,]acetate. Our results support biogenesis of 1 either by intramolecular Diels-Alder cyclization of a C-18 polyunsaturated acid or by the more likely mechanism of intramolecular anionic condensations of a partially reduced C-18 polyketide. Work is in progress to elucidate the biochemical details of the formation of mevinolin (1) and compactin (2).
Laboratories for a generous gift of mevinolin. These investigations were supported by the Natural Sciences and Engineering Research Council of Canada (Grant A0845 and NSERC Summer Studentship to J.K.C.) and the Alberta Heritage Foundation for Medical Research. Registry No. 1, 75330-75-5; acetic acid, 64-19-7; L-methionine, 6368-3.
Supplementary Material Available: Listing of IH N M R data of 1 and conditions for incorporation experiments (1 page). Ordering information is given on any current masthead page.
First Synthesis of Stannacyclobutanes J. W. F. L. Seetz, G. Schat, 0. S. Akkerman, and F. Bickelhaupt*
Vakgroep Organische Chemie, Vrije Universiteit 1081 HV Amsterdam, The Netherlands Received January 31, 1983 Stannacyclobutanes were hitherto unknown, although their synthesis has been attempted and claimed This is all the more remarkable as 1,3-distannacycl~butanes~ and cycl~tetrastannanes~ have been prepared, and germacyclobutanes are well-known.Ib The direct and preparatively useful access to the 1,3-di-Grignard reagent of propane (2a)5 and of its 2,2-dimethyl derivative 2b6 from the corresponding dibromides opens a new approach to metallacyclobutanes. We here report the synthesis of 1,l-dimethylstannacyclobutane ( l a ) and 1,1,3,3tetramethylstannacyclobutane ( l b ) . When a stoichiometric amount of dichlorodimethylstannane (3) was added to 2a at r c " temperature and the reaction mixture was hydrolyzed and subjected to GC-MS, none of the expected l a but only its cyclic oligomers 4a (dimer), 5a (trimer), and 6a (tetramer), formed in about 70% total yield, could be observed.
LE.2
Acknowledgment. We are grateful to G. Aarts and G. Bigam for N M R assistance and to Merck, Sharp and Dohme Research (20) Most assignments were confirmed by selective homonuclear (I3C) decoupling experiments. (21) DeJesus, A. E.; Hull, W. E.; Steyn, P. S.; Van Heerden, F. R.; Vleggaar, R.; Wessels, P. L. J . Chem. Soc., Chem. Commun. 1982, 837-838. Biihler, M.; Keller, P. J.; Eimicke, V.; Floss, (22) Bacher, A.; Le Van, Q.; H. G . J . Am. Chem. Soc. 1982, 104, 3754-3755. (23) (a) Gould, S. J.; Cane, D. E. J. Am. Chem. SOC.1982,104,343-346. (b) Rinchart, K. L., Jr.; Potgieter, M.; Wright, D. A. Ibid. 1982, 104, 2649-2652. (24) (a) Vederas, J. C. Can. J . Chem. 1982,60, 1637-1642 and references therein. (b) Lane, M. P.;Nakashima, T.T.;Vederas, J. C. J . Am. Chem. SOC.1982, 104, 913-915. (c) Hill, J. G.; Nakashima, T. T.; Vederas, J. C. Ibid. 1982, 104, 1745-1748. (d) Nakashima, T.T.; Vederas, J. C. J . Chem. SOC.,Chem. Commun. 1982, 206-208. (e) Nakashima, T.T.; Rabenstein, D. L. J . Mugn. Reson. 1982, 47, 339-343. (f) Smith, G . K.; Mucller, W. T.; Slieker, L. J.; De Brosse, C. W.; Benkovic, S. J. Biochemistry 1982, 21, 2870-2874. (8) De Jesus, A. E.; Hull, W. E.; Steyn, P. S.; Van Heerden, F. R.; Vleggaar, R. J . Chem. SOC.,Chem. Commun. 1982, 902-904. (h) McGarrity, M. J.; King, J. F.; Stothers, J. B. TefrahedronLett. 1982, 23, Cane, 4465-4468. (i) Everett, J. R. Org. Mugn. Reson. 1982, 19, 86-88. D. E.; Liang, T. C.; Hasler, H. J . Am. Chem. SOC.1982,104,7274-7281. (k) Holker, J. S. E.; O'Brien, E.; Moore, R. N.; Vederas, J. C. J . Chem. SOC., Chem. Commun. 1983, 192-194. (25) (a) Staunton, J.; Abell, C. J . Chem. Soc., Chem. Commun. 1981, 856-858. (b) Simpson, T.J.; De Jesus,A. E.; Steyn, P. S.; Vleggaar, R. Ibid. 1982, 632-634. (c) Stoessl, A.; Stothers, J. B. Ibid. 1982, 880-881. (d) Simpson, T.J.; Stenzel, D. J. Ibid. 1982, 89C-892. ( e ) Leeper, F. J.; Staunton, J. Ibid. 1982, 911-912. (f) Simpson, T. J.; Stenzel, D. J. Ibid. 1982, 1074-1076. (g) Jurlina, J. L.; Stothers, J. B. J . Am. Chem. SOC.1982, 104, 4677-4678.
u)
0002-7863/83/1505-3336$01.50/0
Me 4a
Me
5a
6a
Although l a had also been formed, it escaped direct observation with the exception of a singlet in the ' H N M R spectrum when the reaction was performed in dioxane-d8 (6 0.39, ' J s n ~= 52, 54 Hz); due to its characteristic low-field position (cf. lb), this signal must be assigned to the methyl groups of l a . Attempts to isolate l a were thwarted by its high volatility, which prevented its separation from the ether, andby its instability, asit did not surviie the conditions of GC-MS. Compelling evidence for the presence of l a was obtained when the reaction mixture was subjected to distillation at room temperature under reduced pressure. The distillate was treated with a ca. 10-fold excess of 2a, followed by H 2 0 (or DzO) to give 7' (or 7-dz, respectively, Scheme I). Under (1) Gielen, M. Ind. Chim. Belg. 1973, 38, 138. (b) Pant, B. C. J . Organomet. Chem. 1974, 66, 321-403. (2) Bulten, E. J.; Budding, H. A. J . Organomet. Chem. 1979, 166, 339-346. (3) Seyferth, D.; Lefferts, J. L. J . Am. Chem. SOC.1974, 96, 6237-6238; J . Organomct. Chem. 1976, 116, 257-273. (4) Farrer, W. V.; Skinner, H. A. J . Organomel. Chem. 1964, 1,434-436. (5) Seetz, J. W. F. L.; Hartog, F. A,; Bohm, H. P.; Blomberg, C.; Akkerman, 0.S.; Bickelhaupt, F. Tetrahedron Lett. 1982, 23, 1497-1500. (6) Seetz, J. W. F. L.; Schat, G.; Akkerman, 0.S.;Bickelhaupt, F. J . Am. Chem. SOC.1982, 104, 6848-6849.
0 1983 American Chemical Society
